title: Synthesis and anticancer activities of 5,6,7-trimethoxy-N-phenyl(ethyl)-4-aminoquinazoline derivatives.
abstract: A series of 5,6,7-trimethoxy-N-phenyl(ethyl)-4-aminoquinazoline compounds was prepared by microwave irradiation and conventional heating methods. Compounds 6p, 6q, and 6x strongly inhibited extracellular regulated kinase1/2 (ERK1/2) phosphorylation induced by epidermal growth factor (EGF) at 1.28 μM in PC3 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that all compounds had certain anticancer activities, and the IC₅₀ values of 6x were 6.2 ± 0.9, 3.2 ± 0.1, and 3.1 ± 0.1 μM against PC3, BGC823, and Bcap37 cells, respectively. Acridine orange/ethidium bromide staining, Hoechst 33258 staining, DNA ladder, and flow cytometry analyses revealed that 6x induced cell apoptosis in PC3 cells, with apoptosis ratios of 11.6% at 1 μM and 31.8% at 10 μM after 72 h.
authors.affiliation: State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Guizhou University, Guiyang 550025, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Linhong
authors.initials: L
authors.lastname: Jin
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xiang
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Peiyi
authors.initials: P
authors.lastname: Wang
authors.forename: Deyu
authors.initials: D
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.forename: Song
authors.initials: S
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D000091402:Prohibitins; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011799:Quinazolines; D004815:Epidermal Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: (1)H NMR; (13)C NMR; (13)C nuclear magnetic resonance; 10-hydroxyl camptothecine; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; AO/EB; Anticancer; Antiphosphorylation; CH; Cell apoptosis; DMF; DMSO; EGF; EGFR; ERK1/2; ESI-MS; HCPT; IR; MTT; MW; N,N-dimethylformamide; Quinazoline; acridine orange/ethidium bromide; conventional heating; dimethyl sulfoxide; electrospray ionization mass spectrometry; epidermal growth factor; epidermal growth factor receptor; extracellular regulated kinase1/2; infra-red; microwave irradiation; proton nuclear magnetic resonance